Development of a diphtheria toxin mutant conjugate directed against antigen-specific B cells expressing high affinity surface Ig.
Modification of a mutant diphtheria toxin, possessing reduced binding capacity, with TNP groups resulted in an Ag-toxin conjugate capable of eliminating TNP-specific B cells. Previous experimental approaches to the elimination of Ag-specific B cells have involved the conjugation of Ag to holoricin molecules or ricin A chain. Holoricin conjugates possess efficacy, but display high nonspecific toxicity. A chain conjugates, which appear specific, lack high potency. In developing the diphtheria toxin-based conjugate, we found high potency for target anti-TNP hybridoma cells and for spleen cells isolated from TNP-immunized mice. The similar intoxication of nontarget cells required concentrations approximately three orders of magnitude higher. Additionally, it was found that the TNP-specific agent may have selectively depleted B cells producing high affinity IgG anti-TNP antibodies.
Marsh
J W
JW
Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, MD 20892.
Klinman
D M
DM
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000235:genetics; D000922:Immunotoxins; D066298:In Vitro Techniques; D051379:Mice; D009154:Mutation; D014176:Protein Biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism*; D014301:Trinitrobenzenes / Q000276:immunology
D004167:Diphtheria Toxin; D000922:Immunotoxins; D011947:Receptors, Antigen, B-Cell; D014301:Trinitrobenzenes